The epilepsy medicine Valproate is associated with an increased risk of intellectual disability and generally delayed development in offspring, shows new research from Aarhus University Hospital and Aarhus University in Denmark.

Valproate is primarily used to treat epilepsy but also to treat other conditions such as bipolar disorder and migraine. Researchers from Aarhus University and Aarhus University Hospital have now investigated the extent to which children born to mothers taking Valproate during pregnancy experience delayed development and intellectual disability.

The results of the Danish research are published in the scientific journal JAMA Network Open. The results support the previous warning from the medicines authorities on not using Valproate in pregnancy and only in exceptional cases to use the drug in women of child-bearing age.

- The study shows that children born to mothers using the epilepsy medicine Valproate during pregnancy have a 4.5 times increased risk of being diagnosed with an intellectual disability compared with children born to mothers not taking epilepsy medicine during pregnancy, says Julie Werenberg Dreier, Senior researcher at the National Centre for Register-based Research at Aarhus University, who is behind the study.

- When we expanded the outcome by including delayed development together with intellectual disability, the findings showed the risk was six times higher compared with children who had not been exposed to epilepsy medicine during pregnancy, says Julie Werenberg Dreier.

Women with epilepsy should seek medical advice if they wish to get pregnant

The researchers behind the study encourage women with epilepsy to contact their treating physician if they wish to get pregnant.

- Women treated with epilepsy medicine and who wish to get pregnant should contact their treating physician to discuss the risk of medical treatment for epilepsy during pregnancy, says Jakob Christensen who has intensively studied epilepsy for several years. He is a consultant at Department of Neurology at Aarhus University and a Clinical associate professor at Department of Clinical Medicine, Aarhus University

Jakob Christensen underlines that the study should be followed up by further research – preferably internationally – investigating if there are differences between the individual types of epilepsy medicine.

- Intellectual disability is a rare condition – also in children born to mothers treated with Valproat during pregnancy – but this condition is obviously serious. We should pay special attention to children born to mothers who have used Valproat during pregnancy to be able to offer the help these children need.

- We must make sure that pregnant women get the best treatment possible and that Valproat in pregnancy is used in as few cases as possible, says Jakob Christensen. He underlines the importance of finding epilepsy medicine with the lowest possible risk for offspring as many women with epilepsy have to continue their medical treatment for this condition also during pregnancy.

In the period from 1997 to 2016, the researchers followed more than 900,000 children of whom 580 children were born to mothers who had redeemed prescriptions for Valproate during pregnancy.

Unique Danish registries

Using Danish registry data, the researchers have studied the risk among children born to mothers who used the epilepsy medicine Valproat during pregnancy. Previous studies have also concluded that Valproate in pregnancy carries a risk for the offspring; this risk has, however, not previously been compared to the risk among children born to mothers who have not been exposed to epilepsy medicine during pregnancy.

- This type of study assessing the risk in a large group of women who have used medicine during pregnancy can only be conducted in countries with the same organisation of the healthcare system as in Denmark – and where researchers can get access to the data, says Jakob Christensen.

- In this way, research results will benefit the most vulnerable patients and their children; a unique possibility in Denmark of invaluable importance for our patients with chronic diseases.

Behind the research result:

  • A registry-based population study. Between 1997 and 2016, the researchers followed 900,000 children
  • Using Danish registries, the researchers could retrieve data on children with intellectual disability and generally delayed development
  • The research group consists of Christine Aarenstrup Daugaard, Lars Pedersen, Yuelian Sun, Julie Werenberg Dreier and Jakob Christensen – all are from Aarhus University and Aarhus University Hospital
  • The study was supported by the Novo Nordisk Foundation, Central Denmark Region Health Research Fund and the Danish Epilepsy Association
  • Conflicts of interest: Jakob Christensen has received fees for being on an advisory board in the pharmaceutical company Union Chimique Belge (UCB) Nordic and Eisai. Jakob Christensen has also received fees for giving lectures at UCB Nordic and Eisai and he has received travel funding from UCB Nordic. Christine Aarenstrup Daugaard, Lars Pedersen, Yuelian Sun and Julie Werenberg Dreier report no conflicts of interest
  • Link to the scientific article: Daugaard CA, Pedersen L, Sun Y, Dreier JW, Christensen J. Association of Prenatal Exposure to Valproate and Other Antiepileptic Drugs With Intellectual Disability and Delayed Childhood Milestones. JAMA Netw Open. 2020;3(11):e2025570.


Jakob Christensen, Consultant, PhD, DMSc, Clinical associate professor, Department of Neurology, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University
E-mail: jakob@clin.au.dk
Tel.: +45 60 86 58 99

Julie Werenberg Dreier, Senior researcher, PhD
Centre for Register-based Research, Aarhus University
E-mail: jwdreier@econ.au.dk
Tel.: +45 25 62 11 78